Background: Clinical and epidemiological studies have associated selective COX-2 inhibitors with an increased risk of cardiovascular events. There are no clinical studies on the possible effects of these drugs on secondary hemostasis. The hypothesis for this study is that the use of selective COX-2 inhibitors could affect the secondary hemostasis and by that increase the risk of cardiovascular events in a population at high risk.
Methods: An open-label randomized cross-over study was performed in 20 healthy male volunteers. The study consisted of two periods of each 21 days with medication, either celecoxib 100 mg b.i.d. or naproxen 250 mg b.i.d. Treatment periods were separated by a washout period of 28 days. Blood samples were obtained before the first medication period, and at the end of each medication period. Primary effect parameter was FXII level. Secondary effect parameters included a wide range of coagulation factors involved in secondary hemostasis.
Results: There was no statistically significant effect of celecoxib or naproxen on the primary effect parameter. Protein C activity was significantly decreased after treatment with naproxen (P<0.01), compared to baseline. Platelet function, demonstrated as closure time (CT), was at baseline 118+/-24 sec. (mean+/-SD). Naproxen prolonged CT to 171+/-50 sec. (P<0.001). Celecoxib did not change CT significantly (119+/-24 sec.).
Conclusions: Neither the selective COX-2 inhibitor celecoxib, nor the non-selective NSAID naproxen caused any change in the primary effect parameter from the secondary hemostasis.